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FEBS Lett. 2004 Jul 16;570(1-3):138-42.

Analysis of human tumour necrosis factor receptor 1 dominant-negative mutants reveals a major region controlling cell surface expression.

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  • 1Infection and Immunity, University of Wales College of Medicine, Henry Wellcome Research Institute, Heath Park, Cardiff CF14 4XX, UK.


Tumour necrosis factor receptor 1 (TNFR1) plays a critical role in host defence and inflammation. We have identified a membrane proximal region (aa 218-324) of TNFR1 that restricts surface expression. This was prompted by comparing the dominant-negative properties of a C-terminal truncation of TNFR1 with a point mutant that prevents signalling. C-terminal truncation (aa 218-426) generates a better dominant-negative TNFR1 mutant than inactivation of the death domain by point mutation. The increased dominant-negative activity correlates with increased cell surface expression. The membrane proximal region is the most important region of the receptor for restricting expression.

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